Abstract
The chronic and low-grade inflammation induced by obesity seem to be the “first hit” to retinopathy associated to diabetes type 2. Herein, we hypothesized that omega-3 fatty acids from flaxseed oil enriched diet disrupt the pro-inflammatory status in the retina, protecting against retinopathy development. For eight weeks under a high-fat diet (HF), several physiological parameters were monitored to follow the metabolic homeostasis disruption. After this period, mice were treated with a HF substituted in part of lard by flaxseed oil (FS) for another eight weeks. Food behavior, weight gain, glucose and insulin sensitivity, electroretinography, RT-qPCR and western blots were carried out. The HF was able to induce a pro-inflammatory background in the retina, changing IL1β and TNFα. VEGF, a master piece of retinopathy, had early onset increased also induced by HF. The FS-diet was able to decrease inflammation and retinopathy and improved retinal electro stimuli compared to HF group. GPR120 and GPR40 (G Protein-Coupled Receptors 120 and 40), an omega-3 fatty acid receptors, were detected in the retina for the first time. FS-diet modulated the gene expression and protein content of these receptors. Thus, unsaturated fatty acids protect the retina from diabetes type 2 mice model from disease progression.
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Key Findings
In the present study, G-Protein Coupled Receptor 120 (GPR120), the main receptor of ω3, which mediates its potent anti-inflammatory and insulin-sensitizing receptor responses was assessed in the retina. The primary aim of the present study was to determine the presence and functionality of ω3 receptors, GPR120 and GPR40, in the retina on the basal state. The GPR120 and GPR40 mRNAs and protein contents were detected in the retinal tissue of lean mice. However, only GPR120, but not GPR40 was responsive to ω3 stimuli by the β-arrestin2 binding test, in a time-dependent manner (180 min). Hyperglycemia is a determinant factor capable of inducing alterations in the retina structure and, consequently, in the visual acuity. A reduction in the oscillatory potential was evidenced in mice treated with HF-diet, but not in FS, suggesting the compromised visual acuity. The HF-diet induced a pronounced pro-inflammatory state in the retinal tissue, changing the gene expression and protein content of the main pro-inflammatory markers (TNFα and IL1β), and activating the IL10, a homeostatic anti-inflammatory protein. The FS-diet decreased both TNFα and IL1β gene expressions and protein contents. These results describe an essential part of the role of GPR120, a central ω3 fatty acids receptor and the effects of ω3 molecular actions in decreasing the retina’s inflammatory tonus.